A New Guaianolide-type Sesquiterpenoid and Xanthine Oxidase Inhibitory Activity from Chrysanthemum sinense Flowers

The ethanol extract of C. sinense �owers was found to inhibit xanthine oxidase with IC 50 value of 8.20 ± 1.36 µg/mL. Using various chromatographic methods, one new guaianolide-type sesquiterpenoid, chrysanoside K (1), along with seventeen known compounds, cumabrin B (2), angeloylcumabrin B (3), 3 α - chloro-4 β ,10 α -dihydroxy-1 β ,2 β -epoxy-5 α ,7 α H-guai-11(13)-en-12,6 α -olide (4), zawadskinolide B (5), jaceidin (6), quercetagetin 3,6,3(cid:0),4(cid:0)-tetramethyl ether (7), tilianin (8), apigenin 7-O-β -D-glucopyranoside (9), apigenin 7-rutinoside (10), linarin (11), eriodictyol 7-O-β -D-glucopyranoside


Introduction
Chrysanthenum genus belongs to Asteraceae and is native to East Asia and northeastern Europe.They are perennial herbaceous owering plants, sometimes subshrubs.Chrysanthemum sinense Sabine is one of the oriental medicines used since ancient times.Its ower is used to treat fever, rheumatism, in ammation, headaches, eyesight disorder, and cancer.The chemical investigations of this plant indicated the presence of avonoids, caffeoyl quinic acid derivatives, phenolic, and terpenoids (Nguyen et al. 2006).In addition, these compounds exhibited xanthine oxidase inhibitory activity (Nguyen et al. 2006).The ethanol extract of C. sinense owers inhibited xanthine oxidase with IC 50 value of 8.20 ± 1.36 µg/mL.Our ongoing to search for xanthine oxidase inhibitory active secondary metabolites from C. sinense led to the isolation of one new compound and seventeen known compounds.Herein, we reported the isolation, structure elucidation, and xanthine oxidase inhibitory activity of compounds from the owers of C. sinense.

General Experimental Procedures
All NMR spectra were recorded on Bruker 500 and 600 MHz spectrometers (Bruker, Massachusetts, United States).High resolution mass data were obtained from Korea Basic Science Institute (KBSI, Chuncheon Center).Optical rotations were determined on a Jasco DIP-370 automatic polarimeter (Jasco, Tokyo, Japan).UV spectra were obtained from AGILENT 1200 HPLC system (Agilent Technologies, Inc, California, United States).HPLC was carried out using an AGILENT 1100 HPLC system using J sphere H-

Extraction and Isolation
The dried powder owers of C. sinensis (4.5 kg) were ultrasonically extracted with ethanol (EtOH) three times (each 15 L, 30 minutes at room temperature).After removal of solvent, the EtOH extract (1.0 kg) was suspended with water and successively partitioned with n-hexane, ethyl acetate (EtOAc) to give corresponding n-hexane (CS1, 109.0 g), ethyl acetate (CS2, 90.0 g) residues and water layer (CS3).

Xanthine Oxidase Inhibitory Assay
Refer to Supporting Information.

Structural Elucidation
Tables

Figures
Figures

Table 2
The xanthine oxidase inhibitory activity of compounds 1-18 and the extract.

Table 2 .
The xanthine oxidase inhibitory activity of compounds 1 -18 and the extract.Compounds were evaluated at a concentration of 100 μM; $ μg/mL; *Positive control.Data are means of three experiments. #